SUO 2017: A Phase 3 Trial To Compare Efficacy And Safety Of Lenvatinib In Combination With Everolimus Or Pembrolizumab Vs Sunitinib Alone In First-line Treatment Of Patients With Metastatic Renal Cell Carcinoma

Washington, DC ( Introduction: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor alpha, and RET and KIT. Based on a phase 2 study (Motzer et al. Lancet Oncol. 2015), LEN was approved in combination with everolimus (EVE) for the treatment of metastatic renal cell carcinoma (RCC) following 1 prior VEGF-targeted therapy. Dr. Motzer presents a design of a multicenter, open-label, phase 3 trial of LEN plus EVE or Pemborlizumab (PEM) vs sunitinib (SUN); as first-line treatment for advanced RCC.

Methods: Patients aged ≥ 18 years with confirmed advanced RCC diagnosis, ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Karnofsky Performance Status ≥ 70, controlled blood pressure, and adequate blood coagulation, renal, hepatic, and bone marrow function are eligible. Patients will be randomized 1:1:1 to receive LEN 18 mg/d + EVE 5mg/d, LEN 20 mg/d + PEM 200 mg every 3 weeks, or SUN 50 mg/d (on a schedule of 4 weeks on treatment followed by 2 weeks off) until disease progression, unacceptable toxicity, withdrawal of consent, or study end.

The planned primary endpoint is to demonstrate superiority of LEN+EVE or LEN+PEM over single-agent SUN as first-line treatment for advanced RCC in improving progression free survival (PFS). Furthermore, secondary endpoints will include comparison of objective response rate, overall survival, PFS on next-line therapy, health-related quality of life, and safety and tolerability in receiving LEN+EVE or LEN+PEM vs SUN.

Lastly, exploratory endpoints will include PFS in the LEN+PEM arm using immune-related RECIST, comparison of duration of response, disease control rate, and clinical benefit rate in pts treated with LEN+EVE or LEN+PEM vs SUN, and analysis of the relationship between blood biomarkers and outcome. The authors plan to enroll 735 patients to achieve 90% power at 2-sided α = 0.05 to detect a difference in ≥ 1 of the primary comparisons.

Presented by: Robert J. Motzer, New York, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 18th Annual Meeting of the Society of Urologic Oncology, November 29-December 1, 2017 – Washington, DC